This invention relates to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS), also referred to as nuclear magnetic resonance (NMR) imaging and NMR chemical shift spectroscopy, and more particularly, to methods and compositions for enhancing magnetic resonance images and spectra of body organs and tissues.
The recently developed techniques of NMR imaging encompasses the detection of certain atomic nuclei utilizing magnetic fields and radio-frequency radiation and is based on the earlier development of NMR spectroscopy. It is similar in some respects to x-ray computed tomography (CT) in providing a cross-sectional display of the body organ anatomy with excellent resolution of soft tissue detail. In current use, the images produced constitute a map of the distribution density of protons and/or their relaxation times in organs and tissues. The MRI technique is advantageously non-invasive as it avoids the use of ionizing radiation.
While the phenomenon of NMR was demonstrated in 1945, it is only relatively recently that it has found application as a means of spatially imaging the internal structure of the body, as a result of the original suggestion of Lauterbur [Nature, 242, 190, (1973)], and chemically mapping the metabolic status of the body, as a result of the original suggestion of Ackerman et al. [Nature, 283, 167 (1980)]. The lack of any known hazard associated with the level of the magnetic and radio-frequency fields that are employed renders it possible to make repeated scans on vulnerable individuals. Additionally, any scan plane can readily be selected including transverse, coronal, and sagittal sections.
In an NMR experiment, the nuclei under study in a sample (e.g., protons) are irradiated with the appropriate radio-frequency (RF) energy in a highly uniform magnetic field. These nuclei, as they relax, subsequently emit RF radiation at a sharp resonance frequency. The emitted RF energy of the nuclei depends on the applied magnetic field and on the magnetogyric ratio of the specific nuclide under observation.
According to known principles, when nuclei with appropriate non-zero spin are placed in an applied static magnetic field [B.sub.o, expressed generally in units of tesla (10.sup.4 gauss)] they align along the direction of the static field axis, usually taken to be the z axis. In the case of protons, these nuclei precess at a frequency of 42.6 MHz (42.6.times.10.sup.6 Hz or cycles per second) at a field strength of 1 tesla. In this polarized or aligned state, an RF pulse of radiation will excite the nuclei and can be considered to tip or rotate the nuclei out of alignment with the field axis, the extent of this rotation being determined by the pulse duration and amplitude. After the RF pulse, the nuclei "relax" or return to the thermal equilibrium alignment in the static magnetic field, emitting radiation at the resonance frequency. The decay of the NMR signal is characterized by two relaxation times. These are T.sub.1, the spin-lattice relaxation time (or longitudinal relaxation time), that is, the exponential time constant governing the return to thermal equilibrium along the direction of the externally applied static magnetic field, and T.sub.2, the spin-spin relaxation time (or transverse relaxation time) associated with the dephasing of the initially coherent precession of individual proton spins. These relaxation times have been established in the case of proton NMR for various fluids, organs and tissues in different species of mammals.
In MRI, scanning planes and slice thickness can be selected without loss of resolution. This permits high quality transverse, coronal and sagittal images to be obtained directly. The absence of any moving parts in MRI equipment promotes a high reliability. It is believed that MRI has a greater potential than CT for the selective examination of tissue characteristics in view of the fact that in CT, x-ray attenuation coefficients along determine image contrast whereas at least four separate variables (T.sub.1, T.sub.2, nuclear spin density and flow) may contribute to the NMR signal. For example, it has been suggested [Damadian, Science, 171, 1151, (1971)]that the values of the T.sub.1 and T.sub.2 relaxation in tissues are generally longer by about a factor of 2 in excised specimens of neoplastic tissue compared with the host tissue.
By reason of its sensitivity to subtle physio-chemical differences between organs and/or tissues, it is believed that MRI may be capable of differentiating tissue types and in detecting diseases which induce physio-chemical changes that may not be detected by x-ray or CT which are only sensitive to differences in the electron density of tissue. The images obtainable by MRI techniques can in some instances also enable the physician to detect structures smaller than those detectable by CT and thereby provide comparable or better spatial resolution.
Proton or .sup.1 H magnetic resonance imaging has been extensively developed for various applications. Other nuclides such as .sup.23 Na, .sup.19 F and .sup.31 P have also been employed for imaging utilizing MRI techniques. For example, fluorine atoms (.sup.19 F) give a nuclear magnetic resonance signal and, thus, may function as suitable "probes"0 in MRI when combined in a chemically suitable form. There remains a continuing need for further improvements in MRI techniques and methodology.